Towards the end of her training in emergency medicine at Brown University, Rhode Island, Dr Alyson McGregor was asked what her “specialism” would be.
“You are expected to have a niche so my answer was, ‘Well, I like women’s health,’” says McGregor. “From that, people thought, ‘Oh, she’s into obstetrics/gynaecology.’” So on busy shifts in the emergency department of Rhode Island Hospital, the state’s major trauma centre, the newly qualified McGregor became everyone’s go-to doctor for pelvic examinations because this was believed to be her special interest. “I laugh about it now, but it’s when I started to realise that there’s this assumption that women’s health is wrapped up in their reproduction. Women were men with ‘boobs and tubes’.”
But McGregor was interested in far more than that. By women’s health she meant the health of the whole woman, whose female chromosomes exist in every cell and influence every bodily function. She was interested in how these differences – in hormones, in tissue, in systems and structures – impact every disease and the way it should be treated. Cardiovascular health provided her route in.
“This was about 15 years ago when people were realising that women having heart attacks presented differently to men,” she says. “They described different symptoms and had poorer outcomes, so I started to ask why; and if we’re different in this way, what about that way? The more I delved, the more I realised the scope of this. In medicine, we’ve ignored women because we’ve used men as our standard – and it hasn’t served women well.”
McGregor has set this out in her new book Sex Matters. It’s a wake-up call, a cry for action, a frightening and fascinating read. The takeaway message is that women’s bodies are different to men’s from cellular level onwards, yet our medical model is based on knowledge gleaned from male cells, male animals and male humans. Within this, there’s a wealth of disturbing detail – the diseases we routinely fail to understand in women, the drugs that work in men, while being useless, dangerous or even deadly in the other 50% of the population. In an age where we hear talk of “personalised medicine” and “targeted therapies”, it’s impossible to read this book without feeling stunned by science’s failure to have factored all this in earlier. “That’s a common reaction,” says McGregor. “I often hear, ‘Gosh, I thought medicine was taking this into account!’”
We are talking a few weeks before the book’s publication – though Sex Matters certainly won’t have the launch once planned. Instead, McGregor is working long shifts in her emergency department because of Covid-19. (Her husband is a doctor, too – she tweeted pictures of the two of them in their protective gear.) When we Skype on her day off, I ask what life is like right now.
“It’s challenging,” she says. “There’s the anxiety of being home and worrying about my family, and then my family worrying about us at work. And then being at work, but not recognising anyone because we’re all covered up.” The Covid cases in her hospital, says McGregor, are “manageable” and, overall, her patient volumes are down. “The messaging has been, ‘Stay home,’” she says. “Though that makes me worry, too, because where are the heart attacks, the complications from dialysis, the infections? I am seeing people with underlying psychiatric issues seeking care as the pandemic restrictions have increased anxiety and depression for so many.”
In fact, the data on Covid-19 indicates that this, too, is a disease that affects men and women differently. Though many countries, including the US and UK, have been slow to publish detailed sex-specific information, those that have suggested it could have killed up to twice as many men as women. In the UK, an analysis of 4,000 cases by the Office of National Statistics found the same ratio, while figures from New York City Health suggest men account for more than 61% of Covid deaths. Social differences is one possible cause – in China, for example, far more men are smokers. Biological differences is another. Oestrogen helps stimulate the immune system, but the fact that women have two X chromosomes, which contain a high density of immune-related genes, could be key. (Men were also disproportionately affected by Sars and Mers.)
“I’m trying to create a call for all countries to start collecting Covid-19 data by sex so that we can have this knowledge ahead of time,” says McGregor. “In the H1N1 [swine flu] pandemic, it wasn’t until we started looking at sex differences that we realised pregnant women were very susceptible to complications. If we have the information, we can look for explanations and target better treatments. And I’m still not seeing it.”
McGregor believes the reason can be traced back to the beginnings of organised medical research when it was decided that women of childbearing age should be excluded from trials – effectively taking sex differences out of the picture. The reason was to protect them, but for the medical profession and pharmaceutical industry it also made work faster, easier and cheaper by taking out pesky variables such as menstrual cycles and hormone surges. In Sex Matters, McGregor lists multiple ways that today’s drugs can still fail women as a direct result. Women metabolise drugs differently (there are lots of reasons, but many are linked to different hormones and different levels of enzymes), so certain drugs remain in the system for longer or drop to dangerously low levels at certain points of the menstrual cycle. McGregor also shows how common fillers used in generic drugs – which are typically only tested for two weeks in a group of healthy males – can alter bioavailability (how much of the drug that will reach the body and work as planned) in women by up to 24%, which is why she often asks presenting patients if they’ve recently switched to a generic.
One particularly frightening example is the impact of medication on our QT – that’s the resting time between heartbeats. A woman’s QT is already longer than a man’s (a result of men’s teenage testosterone surge) and many prescription drugs – painkillers, antidepressants, antihistamines, antibiotics – cause incremental QT increases as a side-effect. For women on multiple meds (and statistically, women are most likely to be on multiple meds), the risk of these combined increases can range from simple arrhythmia to sudden cardiac death.
McGregor gives the example of one patient, a woman in her 40s whose back pain resulted in a common medication spiral – painkillers then sleeping tablets then steroids then anti-anxiety meds, and finally an antibiotic for a UTI. This cocktail, she believes, caused the patient sudden cardiac death, something she says is “more common than many physicians would like to admit”. One German study found that 66% of long QT syndrome patients were female – and of these, 60% were drug-related.
“Hydroxychloroquine, the drug being trialled as a treatment for Covid [and hyped by Donald Trump], also has the side-effect of prolonging QT interval,” says McGregor. “If it’s prescribed to a female, we should have her QT interval measured first, but that’s not even in the discussion.” In fact, she is concerned that in the race to find a Covid vaccine, reverting to standard research protocols (male cells, male animals and no sex-specific analysis of human trials) could result in dangerous gaps in knowledge.
Some of the areas covered in Sex Matters are already in the public eye. The British Heart Foundation is halfway through a three-year campaign to tackle what it calls the “heart attack gender gap” – a UK woman is 50% more likely than a man to receive an initial wrong diagnosis for a heart attack and, even after correct diagnosis, significantly less likely to receive life-saving treatments. One reason could be that women’s symptoms don’t always fit previous male-centric models. In men, plaque tends to build up, causing blood vessels to rupture. In women, plaque is more likely to gradually erode, making blood vessels stiffer and less flexible over time.
Julie Ward is a senior cardiac nurse with the British Heart Foundation who has worked on the campaign’s All-Party Parliamentary Group. “Coronary care has been male-driven,” she says. “Treated by men using research by men carried out on men. We’re only now beginning to understand the different physiology. Part of our campaigning is to encourage more UK women to sign up for trials, and also to encourage more women to become cardiologists.”
Our treatments for pain are another area where women are poorly served. Epidemiologic studies clearly demonstrate that women are at greater risk of pain conditions – from migraines to musculoskeletal, from IBS to PMS. The interaction between the sex hormones, neurotransmitters, like dopamine and serotonin, and the central nervous system is one key reason (a study of transsexuals undergoing hormone therapy found that half of those transitioning from female to male reported improvements in chronic pain conditions.)
There’s also women’s XX chromosomes that create those aggressive immune responses so effective in fighting disease, but also prone to turn on the body itself (autoimmune diseases, such as lupus and osteoarthritis, are far more common in women). Yet women are more likely than men to receive a psychiatric diagnosis than a physical one (panic attack instead of heart attack), more likely than men to be given lifestyle advice rather than an exploratory x-ray when presenting with IBS – and in the case of “women’s conditions” such as endometriosis, highly likely to be told that the pain they’re experiencing is “normal”. (In the UK, it takes women an average of 7.5 years to get an endometriosis diagnosis – and even then, we’ve developed few effective treatments for this debilitating disease.)
Dr Amanda Williams, Reader in Clinical Health Psychology at University College London agrees that women’s pain is typically downplayed. “Patient studies show it,” she says. “Women are prescribed less analgesic. When a man says he’s in a bit of pain, we think he’s really in a lot of pain. When a woman says she’s in a lot of pain, we think she’s in a bit of pain, but worried about it.”
According to Williams, this can be traced back to Darwinism and the belief in a great “chain of being”, which put men at the top of the hierarchy and women at the lower end. Beliefs about pain reflected power and status. “Black people endured horrendous hardship and brutality so it was said that they were less sensitive to pain, and women endured childbirth, which was pretty painful, so it was believed they were oversensitive, prone to hysterics.” White European men, it was decided, had it just about right.
It’s a bleak picture, but McGregor is confident it’s changing. She is now a recognised sex and gender expert in emergency medicine at Brown (which covers a lot more than pelvic examinations)and has co-founded the Sex and Gender Health Collaborative, a national organisation which works to integrate sex and gender knowledge into medical education and clinical practice. “It has been an interesting evolution,” she says. “When I first started talking about this, no one really understood what I was saying or didn’t quite see the importance. Most physicians are data-driven – and now there’s exponential data coming through that shows how significant sex differences can be. Now I see a different response when I’m speaking. In 2016, the top research funder in the US stated you must include sex as a biological variable in your research design.”
Sex Matters was written to educate and empower the rest of us. “It’s too big to wait for change from the top down,” says McGregor. “If you look at past experiences, it took great grass-roots efforts to have women’s reproductive health taken seriously.”
The book is packed with specific advice for female patients, ranging from volunteering for medical trials to researching sex differences in prescriptions, recording side-effects, joining patient support groups, keeping careful records of symptoms and treatments and taking an advocate along to appointments. She also urges women to be pushier patients. “When a doctor writes a prescription, ask, ‘Is this specific to me as female? Should I have a different dose? Will I have different side-effects? Will this affect my birth control? Should I take a different drug at certain times of my menstrual cycle?’ A doctor may not know those answers – but most people who go to medical school take an oath of lifelong learning. I hope doctors will say, ‘Let me look.’”
Though McGregor believes it can be done in 10 years, the scale of change required seems enormous. “Yes,” she nods happily, “mammoth! I absolutely agree – and I make no apology for that. Each hypothesis is based on the one before and the one before – and if this has all been male, we unfortunately need to start from scratch. But I think it’s a moral obligation we have for half the population.”